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Trends Biochem Sci. 2006 Oct;31(10):581-8. Epub 2006 Aug 21.

Got diversity? Wiring the fly brain with Dscam.

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Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.


The Drosophila gene Dscam, encoding Down syndrome cell-adhesion molecule, is required for the development of neural circuits. Alternative splicing of Dscam mRNA potentially generates 38016 isoforms of a cell-surface recognition protein of the immunoglobulin superfamily. These isoforms include 19008 different ectodomains joined to one of two alternative transmembrane segments. Each ectodomain comprises a unique combination of three variable immunoglobulin domains. Biochemical studies support a model in which each isoform preferentially binds to the same isoform on opposing cell surfaces. This homophilic binding requires matching at all three variable immunoglobulin domains. These findings raise the intriguing possibility that specificity of binding by the Dscam isoforms mediates cell-surface recognition events required for wiring the fly brain.

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